A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells.

Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs may regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent, and selective inhibitors of key ALDH enzymes may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, our structure of human ALDH1A3 combined with in silico modeling identifies a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis reveals that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.

Limited Usefulness of 18F-FDG PET/CT in Predicting Tumor Regression After Preoperative Chemotherapy for Noncardia Gastric Cancer: The Italian Research Group for Gastric Cancer (GIRCG) Experience.

BACKGROUND: The present study aimed to better define the usefulness of F-FDG PET/CT in predicting pathological tumor response (PTR) and survival in patients with noncardia gastric cancer treated with preoperative chemotherapy. METHODS: Seventy-one patients were recruited in 6 Italian centers. The SUV of F-FDG PET/CT was measured at baseline and after treatment, and the difference (dSUV) was computed. The association between PET indexes and PTR, assessed by the Becker score, was evaluated by nonparametric regression. The discriminant power of PET indexes with respect to the absence of PTR (Becker 2/3) was studied by receiver operating characteristic (ROC) curve and synthesized by the area under the curve (ROC-AUC). RESULTS: dSUV allowed to partially discriminate between absence/presence of PTR, when expressed as either absolute value (ROC-AUC, 0.73; 95% confidence interval, 0.59-0.87) or percentage (ROC-AUC, 0.74; 95% confidence interval, 0.59-0.89). However, only extreme values of percent dSUV were really informative. All 7 patients whose F-FDG uptake had increased despite preoperative treatment showed no tumor regression at pathologic examination. Seven of the 10 patients whose metabolic response had been 70% or greater had complete or nearly complete pathologic tumor regression (Becker score 1a or 1b). The metabolic response of the remaining 54 patients, which ranged between 0% and 70%, did not permit to reliably forecast pathologic tumor regression. Survival significantly decreased with increasing Becker score but was unaffected by metabolic response. CONCLUSIONS: The present study suggests that F-FDG PET/CT has limited usefulness in predicting cancer regression. The lack of metabolic response in serial measurements indicates the probable ineffectiveness of preoperative treatment.

Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2.

Plants use leucine-rich repeat receptor kinases (LRR-RKs) to sense sequence diverse peptide hormones at the cell surface. A 3.0-Å crystal structure of the LRR-RK GSO1/SGN3 regulating Casparian strip formation in the endodermis reveals a large spiral-shaped ectodomain. The domain provides a binding platform for 21 amino acid CIF peptide ligands, which are tyrosine sulfated by the tyrosylprotein sulfotransferase TPST/SGN2. GSO1/SGN3 harbors a binding pocket for sulfotyrosine and makes extended backbone interactions with CIF2. Quantitative biochemical comparisons reveal that GSO1/SGN3-CIF2 represents one of the strongest receptor-ligand pairs known in plants. Multiple missense mutations are required to block CIF2 binding in vitro and GSO1/SGN3 function in vivo. Using structure-guided sequence analysis we uncover previously uncharacterized CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK proteins as essential coreceptor kinases required for GSO1/SGN3 and GSO2 receptor activation. Our work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants.

Concomitant screening of coronary artery disease and lung cancer with a new ultrafast-low-dose Computed Tomography protocol: A pilot randomised trial.

We performed a pilot randomised study to assess the feasibility and radiation exposure of a new computed tomography (CT) protocol that allows screening of both coronary artery disease (CAD) and lung cancer. Current or former heavy smokers at high lung cancer risk with indication to cardiac CT for suspected or known CAD were randomised to undergo concomitant CT evaluation of either cardiac or thoracic area or cardiac CT only. Out of 129 subjects deemed eligible for the study, 110 agreed to participate and were randomised to simultaneous cardiac and lung CT (Gr.A; n = 55) or cardiac CT only (Gr.B; n = 55). The feasibility (i.e. adequate visualization of coronary artery segments) was noninferior with simultaneous cardiac and lung CT compared with the standard cardiac CT (870 of 889 segments [97%] in Gr.A vs 878/890 segments [99%] in Gr.B; mean difference 2.0% [90% confidence interval: -0.3% to 4.1%]). The safety (i.e. effective radiation dose) of the concomitant cardiac and lung CT protocol was noninferior to the standard cardiac CT (1.5 [95% confidence intervals: 1.2-1.7] vs. 1.4 [95% confidence intervals: 1.1-1.6] mSv; mean difference 0.1 mSv [90% confidence interval: -0.2 to 0.3 mSv]). In the two groups, a total of 25 significant (>70%) coronary stenoses were found at cardiac CT (9/55 cases of Gr.A vs 11/55 cases of Gr.B). Pulmonary nodules >2 mm were detected in 7 of the 55 Gr.A subjects. This pilot randomised study shows that concomitant CAD and lung cancer screening by means of a new CT protocol is both feasible and safe, thus allowing a comprehensive evaluation of both cardiac and thoracic regions during one CT scanning only. (ClinicalTrials.gov Identifier: NCT03727958).

IntegoTM infusion system: cost effectiveness analysis focusing on dosimetry, sterility and management.

BACKGROUND: Healthcare providers across Europe are facing an ever-growing demand in clinical PET referrals. Currently, it is estimated that the administration of the PET tracer accounts for approximately 40% of the unitary PET procedure reimbursement (uPETr). Although the cost of PET/CT is highly dependent on the radiopharmaceutical cost itself, little is known about the economic impact of the utilized administration method and the repercussions on staff radiation exposure. Our objective was to evaluate the cost-effectiveness of automatic injection/fractionation system Intego™ (Bayer HealthCare, MEDRAD Europe, Netherlands) for istaff radiation exposure reduction and to validate its use with 18F-choline (FCH). METHODS: In order to validate Intego™ use with FCH we analyzed sterility, radioactivity fractionation accuracy and radiation protection for staff. We analyzed Intego™ impact on examination costs and its impact on organization efficiency. A cost-effectiveness analysis (CEA) was estimated as the incremental cost to reduce staff radiationexposure. RESULTS: According to our data, Intego™ ensures both sterility and accuracy of FCH doses' activity, reducing, at the same time, the exposure to radiation either whole body and at the extremities (94% and 75% respectively for the technicians and complete reduction for physicians). Intego™'s variable unit costs are higher than the SA (respectively 1.8% and 0.4% of PET reimbursement), while staff costs are significantly higher with SA (respectively 0.27% and 1.57% of unitary PET reimbursement [uPETr]). In our simulation, based on a 2,450 PET yearly output, the differential costs were slightly higher by using Intego™™ (+ 14%). The incremental cost-effectiveness ratio (ICER) was equal to 1.1, i.e. the healthcare provider pays an additional cost of 0.38% of uPETr to obtain a significant reduction of staff radiation exposure (-4.5 µS). CONCLUSIONS: Intego™, for its favorable results in terms of cost effectiveness, could be a useful tool in a nuclear medicine department, limiting the staff radiation exposure.

Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Reduction of 68Ga-PSMA renal uptake with mannitol infusion: preliminary results.

PURPOSE: Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with 68Ga or 177Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of 68Ga-PSMA. METHODS: Kidney uptake (SUVmax) was calculated in nine patients undergoing 68Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after 68Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after 68Ga-PSMA administration (B-infusion). RESULTS: In patients receiving the A-infusion, mean SUVmax increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUVmax decreased by 24.3% and 22.4% in the right and left kidney, respectively. CONCLUSION: Our preliminary findings indicate that mannitol may play a role in reducing off-target 68Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before 68Ga-PSMA injection. These results warrant dosimetric studies in patients treated with 177Lu-PSMA to find the best scheme for mannitol administration.

Crystal structure of human aldehyde dehydrogenase 1A3 complexed with NAD+ and retinoic acid.

The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD+. The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD+ and the product all-trans retinoic acid (REA). The tetrameric ALDH1A3 folds into a three domain-based architecture highly conserved along the ALDHs family. The structural analysis revealed two different and coupled conformations for NAD+ and REA that we propose to represent two snapshots along the catalytic cycle. Indeed, the isoprenic moiety of REA points either toward the active site cysteine, or moves away adopting the product release conformation. Although ALDH1A3 shares high sequence identity with other members of the ALDH1A family, our structural analysis revealed few peculiar residues in the 1A3 isozyme active site. Our data provide information into the ALDH1As catalytic process and can be used for the structure-based design of selective inhibitors of potential medical interest.

(18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

PURPOSE: We investigated the role of (18)F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). CONCLUSION: This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

Radiation dosimetry of 18F-fluorocholine PET/CT studies in prostate cancer patients.

PURPOSE: We aimed to evaluate the Equivalent Doses (HTs) to highly exposed organs as well as the Effective Dose (ED) for (18)F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients. METHODS: Fifty patients were administered with (18)F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered (18)F-fluorocholine and CT scan, respectively, and the (18)F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure. RESULTS: The calculated (18)F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The (18)F-fluorocholine HTs to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the (18)F-fluorocholine did. CONCLUSIONS: For (18)F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered (18)F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures.

FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy.

PURPOSE: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy. METHODS: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq (18)F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM) iterative reconstruction algorithm. RESULTS: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic), with a median age of 65 years (range: 54-77), were evaluated. Median follow-up was 31 months (range: 4-44). After TP treatment, there was a mean interval of 14 days (range: 9-22) and 125 days (range: 76-162) between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75%) and 3 (37.5%) patients, respectively. CONCLUSION: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax.

Effect of the smear layer on the filling of artificial lateral canals and microleakage

Aim: To evaluate the influence of the smear layer on the filling and prevention of microleakage in artificial lateral canals after use of different irrigating solutions. Methods: Two lateral canals were produced in 44 human dental roots with drills of 0.1 mm in diameter. The roots were divided in 4 groups according to the irrigation protocol: GI - 0.9% saline solution (control); GII - 2.5% sodium hypochlorite + 17% EDTA; GIII - 2% chlorhexidine gel + 17% EDTA; GIV - 2% chlorhexidine solution + 17% EDTA. Four roots were used as negative (n=2) and positive (n=2) controls. Lateral condensation technique and AH Plus were used to fill the root canals. Digital buccolingual radiographs were exposed and after the sealer had set, the roots were immersed in Indian ink dye and then cleared in methyl salicylate. The extent of filling and microleakage were measured and the values analyzed statistically. Results: No difference was found in the percentage of filling and microleakage among the groups, regardless of the location of the artificial lateral canals and the irrigation protocol used. Twenty percent of lateral canals produced no radiographic images, but their filling was confirmed using the clearing technique. Conclusions: The presence or absence of the smear layer did not affect the filling ability and the prevention of microleakage in artificial lateral canals.

Reversible, PET-positive, generalized lymphadenopathy and splenomegaly during high-dose interferon-alpha-2b adjuvant therapy for melanoma.

A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.

Evaluation of in vivo labelled dendritic cell migration in cancer patients.

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with 99mTc-HMPAO or 111In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20-60 min after inoculation and the maximum concentration was reached after 48-72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC.

Role of 18F-FDG PET for evaluating malignant pleural mesothelioma.

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

18F-FDG PET early after radiotherapy in lymphoma patients.

OBJECTIVE: The aim of this study was to evaluate the rate of postactinic inflammatory alterations that could lead to false-positive results in FDG-PET images, in a group of lymphoma patients studied with positron emission tomography (PET) early after the end of radiation therapy. MATERIALS AND METHODS: Sixteen (16) consecutive patients were referred to our center for malignant lymphoma; 14 of 16 patients had a mediastinal bulky mass at diagnosis. Each patient underwent chemotherapy and then radiotherapy (RT): for clinical reasons, shortly after RT (range, 25-56 days; mean, 38.7 days) a FDG PET scan was required to evaluate the effect of therapy. We intravenously injected 370 MBq of 18F-FDG, and after 60-90 minutes we recorded images. RESULTS: Despite a relatively short time after RT, there was no pathological tracer uptake in 13 of 16 patients. In 3 cases, a mild increase in FDG uptake was observed, but no findings which would lead to a false-positive diagnosis. In 2 of 3 cases, postactinic pneumopathy was diagnosed (PET scan performed 51 and 52 days after RT); while in 1 patient, soft-tissue inflammation was present (PET scan performed 42 days after RT). CONCLUSION: Our data indicates that the rate of postactinic PET inflammatory alterations in lymphoma patients is not very high and appear to be not strictly linked to the elapsed time since the end of RT treatment.

Scintigraphic findings in necrotizing myopathy.

Necrotizing myopathy is a rare syndrome associated with several causes, including non-small-cell lung carcinoma. The authors present a case of this infrequently occurring disease, describe an unusual scintigraphic pattern, and show tracer uptake localized in soft tissues rather than the skeleton.

Caracterización de componentes volátiles urinarios mediante perfiles cromatográficos en fase gaseosa (Static Headspace Analysis): aplicación en bioquímica clínica / Characterization of volatile urinary components through gas chromatographic profiles \"Static Headspace Analysis\": biochemical clinical application

Se ha utilizado la técnica de muestreo de la fase vapor en equilibrio con matrices líquidas (Static Headspace Analysis, Static HSA) para el estudio de orinas provenientes de niños normales y de pacientes diabéticos. El análisis de los componentes volátiles extraídos a 80 ñ 2º C se efectuó por cromatografía gaseosa empleando una columna rellena con "Porapak Q". Se demuestra que la expresión gráfica de los resultados mediante "perfiles cromatográficos", constituye una forma rápida de caracterizar y diferenciar individuos normales y diabéticos. Se destacan las ventajas de aplicación de esta técnica para contribuir al diagnóstico de algunas patologías matabólicas